The central theme of the application for a Boston Center for[unreadable] Intervention Development and Applied Research (CIDAR) is "Vulnerability to Progression in[unreadable] Schizophrenia". We see two major strengths of the proposal. First we study subjects who are at various[unreadable] stages of progression of the disorder, prodromal, first episode and chronic, giving us a broad[unreadable] perspective and large database on phenotypic markers and predictors of progression. Moreover,[unreadable] prodromes and first episode individuals will be evaluated in a prospective longitudinal study. A second[unreadable] major strength, in our view, is our plan to link clinical, cognitive, neuroimaging, electrophysiological,[unreadable] hormonal and genetic markers of SZ disease progression to the understanding of how the underlying[unreadable] neural circuits may be disturbed. We do this by investigating the expression of genes of interest in[unreadable] specific cellular populations in post-mortem material and evaluating genetic association of the relevant[unreadable] genes with progression indices from each Project.[unreadable] Four projects, each with an experienced investigator as PI, all evaluate the same group of subjects so[unreadable] as to bring multiple perspectives on the markers and predictors of progression. Project 1. "Functional[unreadable] anatomy of neurocognitive deterioration in schizophrenia", uses neuropsychological and fMRI[unreadable] evaluations. Project 2, "Hormones, memory & sex effects in illness progression in schizophrenia",[unreadable] evaluates hormones and gender differences in schizophrenia. Project 3, "Electrophysiological and MRI[unreadable] gray matter markers and predictors of progression", uses event-related potentials (ERPs) and MRI gray[unreadable] matter measures to evaluate progression, often conjoint, in these two domains. Project 4, "Vulnerability[unreadable] to white matter progression in schizophrenia" uses diffusion tensor imaging evaluations of white matter.[unreadable] A long-standing history of previous successful collaborations and work on joint projects by these project[unreadable] PIs will facilitate the synergistic interactions essential for knitting together data from the different[unreadable] methodological and conceptual domains.[unreadable] The Center mechanism brings added value to this work since no single R01 award could support: 1)[unreadable] the translational gene expression and genetics endeavor in the cores that specifically links to each[unreadable] Project's clinical research findings; 2) the large-scale subject recruiting needed for each project; 3) the[unreadable] extensive neuroimaging work; 4) the linking together of the Project's diverse technologies and levels of[unreadable] analysis on the same subjects, affording a rich opportunity to understand interrelationships of findings[unreadable] from different domains.[unreadable]